Despite a range of available pain therapies, most patients report so-called “breakthrough pain.” Coupled with global issues like opioid abuse, there is a clear need for advanced therapies and technologies for safe and effective pain management. Here the authors demonstrate a candidate for such an advanced therapy: precise and fluid-flow-free electrophoretic delivery via organic electronic ion pumps (OEIPs) of the commonly used anesthetic drug bupivacaine. Bupivacaine is delivered to dorsal root ganglion (DRG) neurons in vitro. DRG neurons are a good proxy for pain studies as they are responsible for relaying ascending sensory signals from nociceptors (pain receptors) in the peripheral nervous system to the central nervous system. Capillary based OEIPs are used due to their probe-like and free-standing form factor, ideal for interfacing with cells. By delivering bupivacaine with the OEIP and recording dose versus response (Ca²⁺ imaging), it is observed that only cells close to the OEIP outlet (≤75 µm) are affected (“anaesthetized”) and at concentrations up to 10s of thousands of times lower than with bulk/bolus delivery. These results demonstrate the first effective OEIP deliveryof a clinically approved and widely used analgesic pharmaceutical, and thus are a major translational milestone for this technology.

The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious micro processing techniques. Here, we report the development of an inkjet printable formulation of polyelectrolyte, based on a custom anionically functionalized hyperbranched polyglycerol (i-AHPG). This polyelectrolyte ink greatly simplifies the fabrication process, and is used in the production of free standing, OEIPs on flexible polyimide substrates. Both i-AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by transport and delivery of the pharmaceutical compound bupivacaine to dorsal root ganglion cells with high spatial precision and effective nerve-blocking, highlighting the applicability of these technologies for biomedical scenarios.

Biological systems rarely use electrons as signal regulators, most of the transport and communication in these system utilize ions. The discovery of conjugated polymers and polyelectrolytes and their unique properties of mixed ionic electronic properties opened the possibility of using these in the domain of bioelectronics, which paved the way for the field of organic bioelectronics. After the introduction of the organic electronic ion pump (OEIP) in 2007, which utilizes both the ionic properties of conjugated polymers and polyelectrolytes, the new field of “iontronics” evolved. TheOEIP is an organic polymer-based delivery system based on electrophoretic transport of biologically relevant and ionically charged species, without fluid flow and with high spatial, temporal, and dosage precision. These devices have been extensivelystudied for the past 14 years and have found numerous demonstrations in in vivo and in vitro delivery of bio-relevant ions for therapeutic application. This has, in parallel, resulted in the development of custom materials for ion exchange membranes (IEMs) within the OEIP.

This thesis focuses on IEMs and device development of OEIPs. Specific focus is given to process development through device design and fabrication through conventional and unconventional technologies. Conventional technologies include microfabrication through photolithography, etching, and thin-film evaporation. Unconventional fabrication techniques include screen printing, inkjet printing, stencil, and laser patterning. In this thesis, we have also scouted a new area of research to utilize the ion-selective properties of polyelectrolytes. Here we discuss a new ion detection technique using IEMs and ion transport based on diffusion coefficients and impedance measurement at a specific frequency using impedance spectroscopy for faster ion detection with low voltage (1–40 V) and liquid-flow-free transport. Further exploring the area of IEMs, we have realized that less attention has been given to stretchable IEMs, even though such materials could find enormous applications in the field of organic bioelectronics and can be used in association with many stretchable electronics applications like stretchable displays and energy storage devices. Current IEMs lack the conformability and stretchability to be used for implantable applications, e.g., including lungs, heart, muscle, soft or brain implants, joints, etc. Keeping this in mind we also discuss our approach for the development of a stretchable IEM. Finally, we focus on developing a hybrid fabrication protocol of flexible OEIPs with micropatterning techniques and inkjet-printed membranes. These OEIPs were fabricated and the functionality was validated by the cell response after the delivery of a nerve-blocking agent to cells in vitro. To date, OEIPs have been fabricated by micropatterning and labor-intensive manual techniques, impeding the budding application areas of this propitious technology. To address this issue, a novel approach to the fabrication of the OEIPs using screen-printing technology is also explored in this thesis. 

In summary, we were able to successfully explore the field of ion-exchange membranesand put forward a new technique for ion detection and stretchable IEMs for future applications. Fabrication of OEIPs was also examined which resulted in the development of a hybrid fabrication protocol with inkjet printing for OEIPs and a robust fully screen printed OEIPs with high manufacturing yield (>90%) for industrial-scale manufacturing.